Predicting the Development of Renal Replacement Therapy Indications by Combining the Furosemide Stress Test and Chemokine (C-C Motif) Ligand 14 in a Cohort of Postsurgical Patients

Abstract

OBJECTIVES: Optimal timing of renal replacement therapy (RRT) initiation in severe acute kidney injury (AKI) remains controversial. Initiation of treatment early in the course of AKI may lead to some patients undergoing unnecessary RRT, whereas delayed treatment is associated with increased mortality. This study aims to investigate whether the combination of the furosemide stress test (FST) and AKI-associated biomarkers can predict the development of indications for RRT. DESIGN: Single-center, prospective, observational study. SETTING: University Hospital of Muenster, Germany. PATIENTS: Critically ill, postoperative patients with moderate AKI (Kidney Disease: Improving Global Outcomes stage 2) and risk factors for further progression (vasopressors and/or mechanical ventilation) receiving an FST. INTERVENTIONS: Sample collection and measurement of different biomarkers (chemokine [C-C motif] ligand 14 [CCL14], neutrophil gelatinase-associated lipocalin, dipeptidyl peptidase 3). MEASUREMENT AND MAIN RESULTS: The primary endpoint was the development of greater than or equal to one predefined RRT indications (hyperkalemia [≥ 6 mmol/L], diuretic-resistant hypervolemia, high urea serum levels [≥ 150 mg/dL], severe metabolic acidosis [pH ≤ 7.15], oliguria [urinary output < 200 mL/12 hr], or anuria). Two hundred eight patients were available for the primary analysis with 108 having a negative FST (urine output < 200 mL in 2 hr following FST). Ninety-eight patients (47%) met the primary endpoint, 82% in the FST negative cohort. At the time of inclusion, the combination of a negative FST test and high urinary CCL14 levels had a significantly higher predictive value for the primary endpoint with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI, 0.82–0.92) compared with FST or CCL14 alone (AUC, 0.79; 95% CI, 0.74–0.85 and AUC, 0.83; 95% CI, 0.77–0.89; p < 0.001, respectively). Other biomarkers showed lower AUCs. CONCLUSIONS: The combination of the FST with the renal biomarker CCL14 predicts the development of indications for RRT.

Performance of urinary C–C motif chemokine ligand 14 for the prediction of persistent acute kidney injury: a systematic review and meta-analysis

“…After removing duplicates, 19 articles were evaluated by their titles and abstracts. Out of these, six studies met the criteria for a full-text review [ 18 – 20 , 24 – 26 ]. During the literature search process, we found that the RUBY study, authored by Hoste et al [ 17 ], and the subsequent secondary analysis article by Koyner et al [ 24 ] shared the same study population.…”

“…To avoid data duplication, we opted to include the more recent study data from Koyner et al, which also provided the target outcome, for our integrated analysis. From the studies conducted by Jiang et al and Meersch et al, in order to reduce the research heterogeneity, we extracted data from subpopulations within those two studies [ 18 , 20 ]. These studies included information on 952 patients, who had data on the incidence of persistent AKI with urinary CCL14 values, and were included in the meta-analysis.…”

“…All six studies were published in the recent three years [ 18 – 20 , 24 – 26 ]. The included number of patients ranged from 18 to 335.…”

“…It is primarily produced by macrophages and monocytes and is thought to play an important role in recruiting immune cells to sites of injury or infection and in regulating inflammation in various organ systems, including the kidney [ 13 ]. The RUBY study and subsequent studies demonstrated that CCL14 levels were significantly elevated in the urine of patients with AKI and elevated urinary CCL14 levels were associated with persistent AKI [ 17 – 20 ].…”

Personalized acute kidney injury treatment

“…If urine output exceeded 200 ml within the consecutive two hours, patients were considered FST positive. The authors demonstrated that a combination of a negative FST test with elevated urinary CCL14 was significantly better in predicting the development of an absolute indication for RRT than FST or CCL14 alone [69 ▪ ].…”